Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload

Backgound: Oxidative stress-mediated, nitric oxide (NO)-dependent vascular endothelial dysfunction develops with aging, increasing the risk of cardiovascular diseases. As such, it is important to identify interventions that can prevent/restore the loss of endothelial function with aging. Caloric restriction (CR) is associated with several physiological benefits and increased longevity in rodents. Some of these benefits are linked to increases in SIRT-1, an enzyme activating endothelial NO synthase (eNOS), and reductions in oxidative stress. We tested the hypothesis that short-term CR would restore vascular endothelial function by improving NO bioavailability and reducing oxidative stress in old B6D2F1-mice, and that this would be associated with increased expression of SIRT-1 and eNOS. Methods: Old (30 months) male B6D2F1-mice were either fed ad libitum (AL, n=6) or were restricted to 70% (3.2g) of their normal food intake for 6 weeks after 2 weeks of progressive restriction (n=6). Carotid artery dilation was assessed ex vivo in response to the endothelium-dependent dilator acetylcholine (ACh) [before and after incubation with the eNOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) or the superoxide dismutase mimetic, TEMPOL] and the endothelium-independent dilator sodium nitroprusside (SNP). Results: ACh-induced dilation was markedly impaired in the AL mice, but was completely restored in the CR mice (63±10% vs. 98±1%, P<0.01). L-NAME decreased ACh dilation by 97% in CR, but only 56% in AL mice, indicating increased NO bioavailability in the CR mice. TEMPOL restored ACh-mediated dilation in AL mice (to 97±1%), but had no effect in CR mice. Aortic protein expression of SIRT-1 and eNOS (western blotting) were 80 –90% higher in CR vs. AL mice (eNOS: 1.9±0.1 vs. 1.0±0.4 P<0.05; SIRT-1: 1.8±0.2 vs. 1.0±0.2, P=0.05). Dilation to SNP was similar in the CR and AL mice (97±1% vs. 96±2%, P=0.63). Conclusion: Short-term CR selectively restores endothelium-dependent dilation in older B6D2F1-mice by increasing NO bioavailability and reducing oxidative stress. These effects are associated with increased vascular expression of SIRT-1 and eNOS. CR may be an effective intervention for reversing age-associated vascular endothelial dysfunction.

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0132 : Oxidative stress and cardio-metabolic alterations induced by postnatal programming can be reversed in adulthood by a short-term moderate caloric restriction

Archives of Cardiovascular Diseases Supplements ◽

10.1016/s1878-6480(16)30381-0 ◽

2016 ◽

Vol 8 (3) ◽

pp. 210

Author(s):

Na Li ◽

Charles Guenancia ◽

Eve Rigal ◽

Olivier Hachet ◽

Corinne Leloup ◽

...

Keyword(s):

Oxidative Stress ◽

Caloric Restriction ◽

Short Term ◽

Metabolic Alterations

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Preconditioning with Short-term Dietary Restriction Attenuates Cardiac Oxidative Stress and Hypertrophy Induced by Chronic Pressure Overload

Nutrients ◽

10.3390/nu13030737 ◽

2021 ◽

Vol 13 (3) ◽

pp. 737

Author(s):

Miyuki Kobara ◽

Nessa Naseratun ◽

Hiroe Toba ◽

Tetsuo Nakata

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Cardiac Hypertrophy ◽

Dietary Restriction ◽

Pressure Overload ◽

Left Ventricular ◽

Public Health Issue ◽

Short Term ◽

Ad Libitum ◽

Mitochondrial Oxidative Damage

Left ventricular (LV) hypertrophy and associated heart failure are becoming a more prevalent and critical public health issue with the aging of society, and are exacerbated by reactive oxygen species (ROS). Dietary restriction (DR) markedly inhibits senescent changes; however, prolonged DR is difficult. We herein investigated whether preconditioning with short-term DR attenuates chronic pressure overload-induced cardiac hypertrophy and associated oxidative stress. Male c57BL6 mice were randomly divided into an ad libitum (AL) diet or 40% restricted diet (DR preconditioning, DRPC) group for 2 weeks prior to ascending aortic constriction (AAC), and all mice were fed ad libitum after AAC surgery. Two weeks after surgery, pressure overload by AAC increased LV wall thickness in association with LV diastolic dysfunction and promoted myocyte hypertrophy and cardiac fibrosis in the AL+AAC group. Oxidative stress in cardiac tissue and mitochondria also increased in the AL+AAC group in association with increments in cardiac NADPH oxidase-derived and mitochondrial ROS production. LV hypertrophy and associated cardiac dysfunction and oxidative stress were significantly attenuated in the DRPC+AAC group. Moreover, less severe mitochondrial oxidative damage in the DRPC+AAC group was associated with the suppression of mitochondrial permeability transition and cardiac apoptosis. These results indicate that chronic pressure overload-induced cardiac hypertrophy in association with cardiac and mitochondrial oxidative damage were attenuated by preconditioning with short-term DR.

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Oxidative Stress as A Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure

Antioxidants ◽

10.3390/antiox10060931 ◽

2021 ◽

Vol 10 (6) ◽

pp. 931

Author(s):

Anureet K. Shah ◽

Sukhwinder K. Bhullar ◽

Vijayan Elimban ◽

Naranjan S. Dhalla

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Angiotensin Ii ◽

Cardiac Hypertrophy ◽

Cardiac Remodeling ◽

Cardiac Dysfunction ◽

Critical Role ◽

Pressure Overload ◽

Hypertrophied Heart ◽

Vasoactive Hormones

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels of several vasoactive hormones including catecholamines, angiotensin II, and endothelins are elevated under pathological conditions, it has been suggested that these vasoactive hormones may be involved in the development of both cardiac hypertrophy and heart failure. At initial stages of pathological stimuli, these hormones induce an increase in ventricular wall tension by acting through their respective receptor-mediated signal transduction systems and result in the development of cardiac hypertrophy. Some oxyradicals formed at initial stages are also involved in the redox-dependent activation of the hypertrophic process but these are rapidly removed by increased content of antioxidants in hypertrophied heart. In fact, cardiac hypertrophy is considered to be an adaptive process as it exhibits either normal or augmented cardiac function for maintaining cardiovascular homeostasis. However, exposure of a hypertrophied heart to elevated levels of circulating hormones due to pathological stimuli over a prolonged period results in cardiac dysfunction and development of heart failure involving a complex set of mechanisms. It has been demonstrated that different cardiovascular abnormalities such as functional hypoxia, metabolic derangements, uncoupling of mitochondrial electron transport, and inflammation produce oxidative stress in the hypertrophied failing hearts. In addition, oxidation of catecholamines by monoamine oxidase as well as NADPH oxidase activation by angiotensin II and endothelin promote the generation of oxidative stress during the prolonged period by these pathological stimuli. It is noteworthy that oxidative stress is known to activate metallomatrix proteases and degrade the extracellular matrix proteins for the induction of cardiac remodeling and heart dysfunction. Furthermore, oxidative stress has been shown to induce subcellular remodeling and Ca2+-handling abnormalities as well as loss of cardiomyocytes due to the development of apoptosis, necrosis, and fibrosis. These observations support the view that a low amount of oxyradical formation for a brief period may activate redox-sensitive mechanisms, which are associated with the development of cardiac hypertrophy. On the other hand, high levels of oxyradicals over a prolonged period may induce oxidative stress and cause Ca2+-handling defects as well as protease activation and thus play a critical role in the development of adverse cardiac remodeling and cardiac dysfunction as well as progression of heart failure.

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Oxidative Stress, Glutathione Metabolism, and Liver Regeneration Pathways Are Activated in Hereditary Tyrosinemia Type 1 Mice upon Short-Term Nitisinone Discontinuation

Genes ◽

10.3390/genes12010003 ◽

2020 ◽

Vol 12 (1) ◽

pp. 3

Author(s):

Haaike Colemonts-Vroninks ◽

Jessie Neuckermans ◽

Lionel Marcelis ◽

Paul Claes ◽

Steven Branson ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Liver Regeneration ◽

The Body ◽

Glutathione Metabolism ◽

Short Term ◽

Therapeutic Regime ◽

Tyrosinemia Type 1 ◽

Hereditary Tyrosinemia

Hereditary tyrosinemia type 1 (HT1) is an inherited condition in which the body is unable to break down the amino acid tyrosine due to mutations in the fumarylacetoacetate hydrolase (FAH) gene, coding for the final enzyme of the tyrosine degradation pathway. As a consequence, HT1 patients accumulate toxic tyrosine derivatives causing severe liver damage. Since its introduction, the drug nitisinone (NTBC) has offered a life-saving treatment that inhibits the upstream enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), thereby preventing production of downstream toxic metabolites. However, HT1 patients under NTBC therapy remain unable to degrade tyrosine. To control the disease and side-effects of the drug, HT1 patients need to take NTBC as an adjunct to a lifelong tyrosine and phenylalanine restricted diet. As a consequence of this strict therapeutic regime, drug compliance issues can arise with significant influence on patient health. In this study, we investigated the molecular impact of short-term NTBC therapy discontinuation on liver tissue of Fah-deficient mice. We found that after seven days of NTBC withdrawal, molecular pathways related to oxidative stress, glutathione metabolism, and liver regeneration were mostly affected. More specifically, NRF2-mediated oxidative stress response and several toxicological gene classes related to reactive oxygen species metabolism were significantly modulated. We observed that the expression of several key glutathione metabolism related genes including Slc7a11 and Ggt1 was highly increased after short-term NTBC therapy deprivation. This stress response was associated with the transcriptional activation of several markers of liver progenitor cells including Atf3, Cyr61, Ddr1, Epcam, Elovl7, and Glis3, indicating a concreted activation of liver regeneration early after NTBC withdrawal.

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Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00744.2010 ◽

2011 ◽

Vol 301 (5) ◽

pp. H2093-H2101 ◽

Cited By ~ 5

Author(s):

Baptiste Kurtz ◽

Helene B. Thibault ◽

Michael J. Raher ◽

John R. Popovich ◽

Sharon Cawley ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Insulin Resistance ◽

Mitochondrial Respiration ◽

Pressure Overload ◽

Lv Remodeling ◽

Stress Levels ◽

Nitric Oxide Synthase 3 ◽

And Function ◽

Oxide Synthase

Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3−/− mice than in SD-fed WT mice. In contrast, HFD-fed NOS3−/− developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3−/− than in those from HFD-fed WT. Nω-nitro-l-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3−/− mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.

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Effects of short-term coenzyme Q10 supplementation on markers of oxidative stress and inflammation after downhill running in male mountaineers

Science & Sports ◽

10.1016/j.scispo.2015.02.012 ◽

2015 ◽

Vol 30 (6) ◽

pp. 328-334 ◽

Cited By ~ 2

Author(s):

L. Abdizadeh ◽

A. Jafari ◽

M. Armanfar

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Short Term ◽

Downhill Running ◽

Markers Of Oxidative Stress ◽

Coenzyme Q10 Supplementation

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Caloric Restriction Reverses Hepatic Insulin Resistance and Steatosis in Rats with Low Aerobic Capacity

Endocrinology ◽

10.1210/en.2010-0176 ◽

2010 ◽

Vol 151 (11) ◽

pp. 5157-5164 ◽

Cited By ~ 30

Author(s):

Thomas A. Bowman ◽

Sadeesh K. Ramakrishnan ◽

Meenakshi Kaw ◽

Sang Jun Lee ◽

Payal R. Patel ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Caloric Restriction ◽

Visceral Obesity ◽

Insulin Clearance ◽

Hepatic Insulin Resistance ◽

The Metabolic Syndrome ◽

Cell Adhesion Molecule 1 ◽

Muscle Triglyceride

Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2–3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.

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